Heartburn is the most frequent symptom of gastrointestinal origin. Despite many published observations, how and why it occurs--and does not occur more frequently--are largely unknown. Until we know some of these hows and whys, treatment of this symptom must remain empirical--neither rational nor highly effective. This proposal--a logical outgrowth of Grant AM-11907--would seem to have an excellent chance of providing some of the necessary answers. We have characterized the increase in lower esophageal sphincter (LES) pressure that accompanies an increase in gastric pressure. The mechanism of this esophagus-protecting effect is unknown, but the increase in LES pressure has been shown to be intrinsic to the sphincter, not the result of external compression. We will determine if (as seems likely) this effect is a reflex and, if so, where the receptor site is located and its physiologic stimulus. We shall also extend our observation that the hormone gastrin has a profound effect on LES strength. These studies will include determination of dose-response relationships for both exogenous and endogenous gastrin and the effect of meals of various composition on LES strength. Subjects having a clinically normal LES and patients having a clinically incompetent LES will be studied.